Abstract

The study of correlated mutations in alignments of homologous proteins proved to be successful not only in the prediction of their native conformation but also in the development of a two-body effective potential between pairs of amino acids. In the present work, we extend the effective potential, introducing a many-body term based on the same theoretical framework, making use of a principle of maximum entropy. The extended potential performs better than the two-body one in predicting the energetic effect of 308 mutations in 14 proteins (including membrane proteins). The average value of the parameters of the many-body term correlates with the degree of hydrophobicity of the corresponding residues, suggesting that this term partly reflects the effect of the solvent.

Article outline:I. INTRODUCTIONII. DERIVATION OF THE POTENTIALIII. EFFECT OF THE MANY-BODY TERM ON THE PREDICTION OF THE EXPERIMENTAL ΔΔGIV. ROLE OF THE PARAMETERS OF THE MODELV. PROPERTIES OF THE η-TERMVI. CONCLUSIONS